Porous product mold form

ABSTRACT

The present invention is directed to apparatus and methods for forming open-cell porous mold forms to mold porous devices having substantially continuously interconnected pores. The mold form is made from selected material comprising particles having predetermined sizes and shapes which is capable of forming a stable mold form under selected conditions. The particles are treated such that the particles are manipulable into a mass of continuously interconnected particles defining continuously interconnected pores and connecting interstices within the mass. The formed mass is made into a predetermined shape and solidified to form a mold form.

This application is a divisional of application U.S. Ser. No.08/156,675, filed Nov. 22, 1993, which is a continuation of U.S.application Ser. No. 07/779,387, filed Oct. 18, 1991, now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to a device, at least a portion of whichis porous, for use as a prosthesis, treatment implement, and otherutility, and a process of fabricating such device.

The applications and uses of synthetic biocompatible implements anddevices adapted for implantation or installation in or on a human bodyhave dramatically increased in recent years. Such implements and devicesinclude soft tissue implants for use, for example, in breastaugmentation, chin, nose, ear and other body part reconstruction and thelike, nerve cuffs and scaffolds, lymphedema shunts, percutaneous skinand blood access devices, insulin cell producing implants and other cellsequestrating cage devices, artificial tendon and ligament and tendonand ligament repair prostheses, artificial heart and vascularprostheses, burn dressings, and drug infusing, releasing or deliverydevices.

Oftentimes, devices of the type described above fail due to problems atthe implant-tissue interface. As early as 1970, Homsey, recognized thatif the implant size is in the order of centimeters, a"fibrocartilaginous" membrane or capsule isolates the implant fromnormal tissue. If the implant is perforated so that the interstices(pores and pore interconnections) are of the order of 1 mm or less, theimplant becomes woven with the tissue, rather than encapsulated as above(Homsey, C. A., 1970, J. Biomed. Mater. Res., 4:341-356). Smooth-walledsilicone breast implants fail in the order of 40-60 percent due to thisthick "fibrocartilaginous" membrane (capsule) which forms around theimplant creating a hard, inelastic, and often painful feeling implant.This fibrous capsule also creates other problems around implants ingeneral because it is composed mainly of dense compacted collagen, andfibroblasts, with little or no vascularity. This leads to isolation ofthe implant, the implant-capsule interface, and the capsule itself fromthe nutrient, metabolic, and cellular advantages of good blood supply,making the implant site more prone to infection, and the infections lessamenable to treatment by natural resistance mechanisms and/or bloodborne antibiotics.

Porous devices known under the trade names Ivalon Sponge(polyvinylchloride) and Ashley breast prosthesis (polyurethane) werecreated to allow tissue ingrowth into the pores within the implant.These devices were totally porous, sponge-like devices which didn'tlimit the tissue ingrowth into the pores or limit implant access tobodily fluids and, with nothing to stop or control such ingrowth orfluid access, poor quality ingrown tissue, with interior calcificationand hardening, resulted. Such hardening is not only uncomfortable to therecipient but also unnatural in appearance and function.

In an attempt to solve some of the above problems, at least with breastprosthesis, polyurethane foam covered silicone rubber breast protheses,both with and without a silicone shell surrounding gel, were developed,but with mixed results. For the prostheses using a silicone shell, thepolyurethane foam was mechanically fixed to the shell with siliconeadhesive. However, the interface between the foam and shell was weak andoftentimes resulted in delamination, sometimes with leakage of thesilicone gel into the surrounding tissue. For the prostheses notutilizing a silicone shell, the gel would typically leak or "bleed"through the polyurethane cover into the surrounding tissue. Such"contamination" of the surrounding tissue with the gel caused localinflammation and gel migration to distant organs. Also, because of thethree-dimensional interlocking nature of the pores within thepolyurethane foam, the relatively inelastic nature of the polyurethane,and the large ratio of ingrown tissue compared to the amount of materialin the foam, a "Chinese handcuff" type situation (ingrown tissue lockedwith foam) was created with the tissue, making it very difficult toremove or change the prostheses. Further, polyurethanes, as a class, arebiologically unstable and will chemically degrade, giving rise tostructure breakdown, sometimes with severe inflammation. A recentconcern with such chemical degradation is the potential for release oftoluene diamine (TDA), a chemical which, even in small amounts, is knownto cause cancer in laboratory animals.

Previous approaches to forming porous materials (for implants or otheruses) have typically included use of bubble-forming technology,sintering of metal or polymer particles into a partially fused body,expansion of polymer melts or solutions (such as used to produceGortex), processing fibers to produce fabric felts, velours, meshes orweaves, and replicating or duplicating the microstructure of carbonateanimal skeletal material. See, for example, White, R. A., Weber, J. N.and White, E. W., "Replanineform: A New Process for Preparing PorousCeramic, Metal, and Polymer Prosthetic Materials," Science, Vol 176, pp922-924; U.S. Pat. No. 3,890,107; Leidner, J. et al., "A Novel Processfor the Manufacturing of Porous Grafts: Process Description and ProductEvaluation," Journal of Biomedical Materials Research, Vol. 17, pp.229-247 (1983). Among the problems of using bubble technology to produceporous materials is the difficulty of separately controlling pore size,pore shape, and pore interconnections. Also, the resulting porestypically include sharp edges and terminations which can causeaccelerated inflammation and thus problems and/or discomfort whenimplanted. The sintering and polymer expansion approaches are limited tothe use of only certain kinds of materials, typically metals forsintering and polytetrafluoroethylene for polymer expansion, and thesemay not be materials having the desired flexibility, resiliency,biocompatibility, or the like. The processing of fibers is limitedbecause only materials which can be made into fibers can be used, andthe resulting structure is basically two-dimensional. The replication ofcarbonate animal skeletal material, although suitable for some uses,requires milling of the material to the desired size and shape, andagain the pore size and shape cannot be controlled.

Two recently issued patents, U.S. Pat. Nos. 4,859,712 and 4,889,744,disclose the use of dissolvable particles initially placed on uncuredsilicone, curing the silicone, and then dissolving the particles toyield a silicone product having a purportedly open-cell porous surface.The particles mentioned in both patents as the preferred solid solubleparticles are crystalline sodium chloride (salt) and no other exemplaryparticles are identified. A number of problems or difficulties arepresent with the methods disclosed in the two patents including thedifficulty of obtaining a completely open-cell structure since the saltparticles are simply placed in the surface of the implant before curing,and then the implant is cured and the salt particles dissolved. Sincemany of the particles will not touch, a mostly closed-cell section isproduced except at the surface layer. With this technique, it is alsodifficult, if not impossible, to premold the solid particles intopredetermined desired shapes (since salt particles do not hold togetherand therefore cannot be molded), and the depth of the porous portion,and the size and shape of the structural interconnections surroundingthe individual open cells cannot be controlled (since salt crystals canonly be pressed into contact with one another but do not inherentlystick together).

Since the treatment possible with the approaches disclosed in the abovetwo patents is only at the surface and doesn't extend in a truethree-dimensional direction, the fibrous capsule created afterimplantation has essentially the same thickness and density as with asmooth surfaced implant. A true three-dimensional unitary poroussilicone rubber prosthesis has not been available until the technologyof the present invention was developed.

SUMMARY OF THE INVENTION

It is an object of the invention to provide a new and improved open-cellproduct, and process for constructing same.

It is another object of the invention to provide such a process in whichthe degree of porous versus nonporous portions of the product can beseparately controlled.

It is a further object of the invention to provide such a process inwhich the size and shape of pores of the open-cell product can bepredetermined and controlled.

It is an additional object of the invention to provide such a process inwhich the size and shape of the entire porous portion of a partiallyporous product can be controlled.

It is also an object of the present invention to provide a process andresulting product in which the porous portion and the non-porous portionof the product are made in a unitary fashion, without an interfacebetween the two portions.

It is still a further object of the invention to provide such a processand resulting product which, when used as a body implant, serves toreduce or eliminate calcification, hardening and fibrous capsularformation, and to promote new loose tissue and new vessel ingrowth tothereby increase recipient acceptance of the prosthesis.

It is still another object of the invention to provide such a processand product in which the resulting pores of the porous part of theproduct are free of sharp edges and terminations to thus increaseacceptance by a patient when implanted or applied to a body part ororgan.

The above and other objects of the invention are realized in a specificillustrative method of preparing a device of a selected material to havepores and pore interconnections of predetermined sizes and shapes. Themethod includes the steps of forming a selectively removable open-cellporous mold form (SRO-CPMF) comprising particles which adhere togetherand have sizes and shapes corresponding to the desired pore sizes andshapes, and particle connections which bind the particles together inthe desired form, where the particle connections correspond to thedesired sizes and shapes of the pore interconnections. The vacancies orvoids between the particles of the mold form are then filled with theselected material, the material converted to its solid form, for exampleby polymerization, and the mold form is removed, for example bydissolution, to thereby leave the selected material in place. Theresulting porous device includes pores and pore interconnectionscorresponding in size and shape to the particles and particleconnections respectively, as desired.

Examples of materials suitable for the resulting porous device includepolymers, metals, metal alloys, ceramics, biological derivatives, andcombinations thereof, in solid or fiber form. Examples of materialssuitable as mold material for forming the SRO-CPMF include sugar,thermoplastic polymers such as waxes, paraffin, polyethylene, nylon,polycarbonate, or polystyrene in naturally available particles orprocessed into specific sizes, shapes, molded forms, spheres or fibers,salt or other particles which cannot be made to inherently sticktogether coated with sugar, and certain drug crystals such asgentamycin, tetracycline, or cephalosporins. In general, anydissolvable, burnable, meltable, or otherwise removable particle whichcan be made to stick together could be used.

Many particles are available from manufacturers in a wide range of sizes(or shapes) such as, for example, polystyrene spheres. Where specificsizes, shapes or forms of a material are not available, they may becustom formed. In the sugar example, the sugar may be heated with cornsyrup and cooked to cause the mixture to polymerize and form hard-tack.While still hot and in its liquid form, this mixture may be poured intomolds, extruded into fibers or injection molded into specific shapes, orcooled and crushed into sized particles. Similarly, any thermoplasticpolymer may be processed for specific sizes or shapes, any of whichcould be used for an SRO-CPMF.

With the method of the present invention, the surface terminations ofthe porous portion of a structure are generally smooth and rounded,unlike terminations of porous portions constructed with prior artmethods. The pores of such porous sections may also vary in size notonly from pore to pore, but also from one portion of the pore section toanother portion. Such porous sections may also be formed to extend to aselected depth in the structure, or all the way through the structure ifthat is desired.

DESCRIPTION OF THE DRAWINGS

The above and other objects, features and advantages of the inventionwill become apparent from a consideration of the following detaileddescription presented in connection with the accompanying drawings inwhich:

FIG. 1 shows a side, cross-sectional view of a container in which isdeposited sugar mold material for making a porous material product, andan enlarged view of a portion of a solidified sugar mass, in accordancewith the principles of the present invention;

FIGS. 2A, 2B and 2C show fragmented, cross-sectional views of a sugarmass in a container, and resulting final porous products, respectively;

FIGS. 3A and 3B show an elevational, cross-sectional view of a containerwith sugar mold material and final product material, and an elevational,cross-sectional and fragmented view of the final product, respectively;

FIG. 4 shows an enlarged cross-sectional, fragmented view of finalproduct material which includes fiber fragments, in accordance with thepresent invention.

FIGS. 5A, 5B, 5C and 5D show elevational, cross-sectional views of amold container shown in the open position, two closed positions,suitable for use in accordance with the process of the presentinvention, and a final product, respectively;

FIG. 6 shows a side, cross-sectional view of a product having top andbottom porous sections with a middle, nonporous section;

FIGS. 7A, 7B and 7C show cross-sectional views of a mold container withan implant model, a mold container filled with the final productmaterial, and the resulting final product implant, respectively;

FIGS. 8A, 8B, 8C and 8D show elevational, cross-sectional views of amold container for constructing a mold form, the mold form with thefinal product material applied, and two versions of the finalprosthesis, respectively, in accordance with the present invention;

FIG. 9 shows an elevational, cross-sectional and fragmented view of aprosthesis for use as a drug delivery implant;

FIG. 10 is a side, cross-sectional view of a porous metal alloy productmade in accordance with the present invention;

FIG. 11 shows a cross-sectional and fragmented view of a doubly-porousprosthesis, with mold form still in place, made in accordance with thepresent invention;

FIG. 12 shows a cross-sectional, fragmented view of a final porousproduct with a coating of material on the pore surfaces, made inaccordance with the principles of the present invention; and

FIG. 13 is a side, cross-sectional, fragmented view of two interlockingmaterials produced in accordance with the present invention.

DETAILED DESCRIPTION

In carrying out the process of constructing porous or partially porousproducts in accordance with the present invention, a first step issimply to select the mold material for use in forming the selectivelyremovable open-celled porous mold form (SRO-CPMF) from which the finalproduct will be molded. Such mold material, advantageously, is readilyavailable, inexpensive, and resistant to dissolution by the liquid form(or the dissolved or dispersion form) of final product material. Also,the mold material should be available in selectively sized and shapedparticles which may readily adhere together (or be made to adheretogether) to thereby assure a continuous and entire open-cell productwhen the mold material is removed or dissolved away. Finally, the moldmaterial, when in the mold form, should be readily removable withoutsignificantly altering the final product (or product material). Thisremoval may be by dissolution by some solvent which does notsignificantly dissolve the final product material. Alternatively, themold material may be melted (or burned) out of the final productmaterial if the melting point (or burning point) of the mold material isbelow that of the final product material.

The final product material likewise would be selected to have thedesired characteristics, for example, flexible and resilient for someapplications in which case silicone rubber might be selected, and rigidin other applications in which case a polyester resin, epoxy resin,metal or metal alloy or ceramic may be selected.

In the first example to be discussed, a partially porous device will bedescribed, as well as a method of controlling the location of porous andnonporous sections. In this illustrative embodiment, sugar is selectedas the mold material or SRO-CPMF, and silicone rubber is selected as thefinal product material.

Sugar may be obtained with fairly uniform particle size and facetedcrystal shapes and, if even greater uniformity of size is desired, thenthe particle size may be selected using standard screen-sizingtechniques.

Once the desired particle size and size distribution for the sugar moldmaterial are obtained, the sugar particles are mixed with de-ionized orpurified water in a volume ratio of from 8 to 25 parts sugar to 1 partwater. If a higher percentage of porosity in the final product isdesired, then more water is added to the mixture to produce greatersurface contact and fusing of the sugar particles, and this, in turn,produces more numerous and larger pore interconnections. A lowerpercentage of porosity in the final product is achieved by using lesswater, thus resulting in less contact and more space between theSRO-CPMF particles. If a larger pore size in the final product isdesired, a larger particle size is chosen. Conversely, if a smaller poresize in the final product is desired, a smaller particle size is chosen.

The sugar and water are thoroughly mixed until all of the sugarparticles have been contacted by the water and to some extent partiallydissolved resulting in a saturated sugar solution (no more dissolutioncan take place). When the desired consistency is reached and the mixtureis stabilized, the resulting moist semi-solid mass (moldable mass) maybe molded into any desired shape by placing it in a pre-shaped mold andallowing it to solidify into the mold form, i.e., allowing or causingthe water within the mold form to evaporate and the sugar in solution torecrystallize and precipitate on and between the sugar particles. FIG. 1shows a cross-sectional view of a conventional cylindrically-shapedcontainer 4 in which is deposited a moistened mass of sugar 8. Section12 of the sugar mass represents a magnified portion of the sugargranules 15, with the voids 16 between the granules.

Solidification of the moldable mass into the SRO-CPMF may be acceleratedby supplying dry air (which may be heated) to the mass, for example.Freezing, freeze drying or vacuum desiccation, with or without addedheat, may also be utilized to cause the mass to solidify. Enlarged view12 of the SRO-CPMF shows the sugar granules or particles 20 fusedtogether, leaving voids 16 between the particles.

After solidification, the sugar mold form may either be left in place inthe container 4 (FIG. 1) or removed from the container 4 (as will be thecase in the FIG. 3 description hereafter), depending on the nature ofthe final product desired. For example, by leaving the sugar mold formin the container 4, the mass will maintain contact with and adhere tothe container walls 24 (FIG. 2A) so that supply of the final productmaterial to the mold form (to be described momentarily) will result in aporous surface 28 in the final product (FIG. 2B), with the surface pores30 being formed by the sugar particles 26 of the mold form (FIG. 2A) incontact with the container wall 24. On the other hand, if the sugar moldform 8 is removed from the container (or the adherent surface at thecontainer wall is eliminated) and the final product then supplied to themass, for example, as it is held in a larger container 38 (FIG. 3A), thesurface exterior 40 (FIG. 3B) of the final product (covering the sugarmold form) will not have pores. FIG. 3B shows this nonporous surfacearea and section 40, with a porous interior 42; the thickness of thisnonporous section 40 will depend upon the quantity of final productmaterial applied to the outside of the mold form.

Another illustrative method for forming the SRO-CPMF involves placingpure sugar particles of the desired size in a metal container and thenheating the particles slowly to slightly below or just at the sugarmelting point. While this is being done, the sugar particles arecompressed and forced to contact each other, and then the mass isallowed to cool. The more the sugar particles are compressed together,the more numerous and larger will be the size of the particleconnections, the more dense will be the SRO-CPMF, and the greater willbe the percentage porosity of the porous portion of the final product,and vice versa. After cooling, the mold form may either be removed fromthe container or left in contact with the container as discussed above.

After the sugar mold form is completed, a medical grade silicone rubberis catalyzed, mixed and de-bubbled in a conventional manner to achieve aliquid state and to prepare the silicone rubber for subsequentpolymerization, i.e., conversion from liquid to solid state. Theprepared, catalyzed silicone rubber is then forced into and through theinterstices or pores of the sugar mold form for example by pressureapplication to the silicone rubber, vacuum application to the mold form,gravity flow, mechanical agitation or a combination of these techniques,all of which are well-known. The thickness of the porous portion of thefinal product can be less than or equal to the thickness of theSRO-CPMF. This can be specifically controlled by controlling the depthof penetration into the SRO-CPMF of the liquid form of the final productmaterial. If the liquid is forced to completely penetrate the mold form,the specific thickness of the SRO-CPMF itself can be used to control thethickness of the porous portion of the device.

Following supply of liquid silicone rubber to the mold form, thesilicone rubber is allowed (or caused) to polymerize after which thesugar mold form is dissolved by a suitable solvent (in this casede-ionized water) and agitation. What is left after this step is thedesired silicone rubber final product. A number of washings may berequired to completely remove all of the residual sugar and ultrasonicwater baths or other agitation is especially effective to do this. Also,hot de-ionized water or steam rinses could be utilized, after which thefinal product would be dried.

If the combined structure of the SRO-CPMF and final product material wasdeveloped by removing the mold form from the container before applyingthe final product material to the mold form, FIG. 3A then a coating offinal product material would surround the mold form resulting in anonporous covering 40 so that there would be no access for the solventto reach and dissolve the mold form 8 (FIG. 3A). In this case, a smallportion of the final product material would be removed at a surfacelocation to allow access of the water solution to the interior.Alternately, needle penetration of the solid product material 40 couldprovide the desired access for the water solution, and removal of thedissolved sugar.

The thickness and shape of a nonporous surface portion of a finalproduct can be readily adjusted by standard molding or injection moldingdie techniques such as by selecting an appropriately sized and shapedcontainer in which to place the mold form and then filling the containeror mold with the unpolymerized silicone rubber. If the SRO-CPMF occupiesonly a small volume of the container, then the thickness of thenon-porous portion of the final product will be great. The size andshape of the non-porous portion of the final product is determined bythe size and shape of the container in which the mold form is placedless the size and shape of the mold form placed in the container.

The shape and the amount of the porous portion of the final product willbe determined by the shape and the portion of the mold form filled withthe final product material. Any portion of the mold form not filled withthe final product material will result in a void 142 in the finalproduct (see FIGS. 8C and 8D). The position of the porous portionrelative to the non-porous portion of the final product will bedetermined by the placement of the mold form within the mold.

Except in a case to be described later (where a gas is forced throughthe mold form), one portion of the surface of the final product materialwill be non-porous. This portion corresponds to the location ofintroduction of the liquid form of the final product material into themold form. By controlling the adherence of the mold form to thecontainer or mold surfaces, the completeness of penetration of theliquid form into the mold form, and by controlling which surface areaand the size of that surface area at which the liquid form of the finalproduct material is introduced into the mold form, the location of theopened-cell surfaces and the location of the non-porous surfaces may becontrolled. For example, a product made into a sheet may be entirelyporous on the lower surface and non-porous on the upper surface. As anexample using the adherent container wall 4 to the mold form 8 in FIG.1, this would be done by introducing the final product material tocompletely penetrate the mold form 8 on its entire upper surface,keeping the lower surface of the mold form adherent to the containerwalls. Alternatively, the final product material could be applied topenetrate only partway into the mold form. Either example results in apartially porous final product (FIG. 2C) with a nonporous upper surface32, and a porous portion 34, with porous surfaces on the sides andbottom of the porous portion 34. However, if the final product materialis introduced from the side, with an otherwise adherent (to all thecontainer walls) mold form within the rest of the mold, the upper andlower surfaces of the sheet, as well as the sides where the liquid isnot introduced will be porous. In this manner, the surfaces of theporous portions versus non-porous surface portions of the device can becontrolled.

The final silicone rubber product which is at least partially porous iscured (polymerized), for example, in a drying oven for 15 minutes to 1hour at a temperature ranging between 275 degrees F. and 425 degrees F.,depending upon the specific silicone rubber used. The final product canbe further formed or sculpted by cutting or adding to the product or bygluing other solid or porous silicone rubber parts or materials.However, the advantage of the method of the present invention is thatrarely would one need to cut, glue, sculpt or add to the final product,since the variables between the porous and non-porous portions can beseparately controlled. Cutting, gluing and sculpting, etc. also addinterfaces and irregularities, stress risers and contour defects. In themethod of the present invention, the porous and the non-porous portionsof the device can be unitary, without interfaces, defects or contourirregularities. Standard packaging and sterilization procedures can thenbe performed if desired.

With the above-described process for forming open-cell porous products,complex shapes, forms and sizes may be readily fabricated. Also, thereis no limitation as to the location of the porous portions of theproduct as there is with prior art methods.

A second example of the present invention will now be described in whichthe pore size of the porous portion of the final product will vary.Initially, small particles of sugar (e.g., 50-75μ) are placed in acontainer to a depth of, for example, 0.2 mm. Another size range ofparticles of sugar (e.g., 100-150μ) are then placed to another specifieddepth, say 0.3 mm, over the first layer. This is continued until a finallayer is added, say 200-300μ particles size, for a depth of 0.6 mm. TheSRO-CPMF particles in the container are then made to stick togethereither by adding a saturated solution of sugar to all of the particlesand draining it off the bottom by vacuum, or by exposing the containerand graduated sized particles to near 100 percent humidity for 15minutes to 4 hours, and then allowing the SRO-CPMF to dry (harden).Alternatively, the particles may be heated just to the melting point,compacted and cooled as described previously. The SRO-CPMF is thenfilled with the liquid form of the final product material as previouslydescribed-here silicone rubber. The resultant product is a partiallyporous device where the porosity varies selectively or continuously asdesired, from one area to another. This is illustrated in FIG. 3B wherethe pore size varies from smaller to larger in the direction away fromthe nonporous section 40.

With the above-described method, many useful devices have been produced,such as vascular graft prostheses made from medical grade siliconerubber, Biomer, and Biolon (medical grade polyurethanes). Theblood-facing surface of vascular devices have been constructed as abovewith pore sizes of 25μ, 50μ, 75μ and 100μ. The porosity through the restof the product may range from 30μ to 300μ, with a wall thickness 1/2 to2 mm. Cell cultures of endothelial and smooth muscle cells have beengrown on the blood-facing surface of the device, where the porosityassists the attachment and, subsequently during implantation, theporosity adds to the nutrition of these cells during and after theingrowth of tissue and neovascularity.

With larger pore sizes (50μ to 100μ) on the blood-facing surface ofvascular grafts, pre-clotting the graft is necessary. After tissueingrowth, the neovascularity may support neointimal cellularregeneration on the blood-facing surface of the device with or withoutcell culture seeding.

The vascular prostheses described above may be implanted intosubcutaneous or intra-muscular positions. After the prosthesis wallsbecome filled with tissue (from several minutes [pre-clotting] toseveral days [cell seeding] to several weeks [tissue ingrowth] dependingon the type of tissue desired), the prosthesis may be removed from itsposition and transplanted as a composite (composed of two types ofmaterial--tissue and polymer) graft into the recipient site, in thiscase a blood vessel. In this way, a vascular graft composed of tissue(as well as polymer) can be used as a live autogenous graft withoutcreating the donor-site morbidity of sacrificing a blood vessel. In asimilar fashion, many types of tissue may be transplanted including bonemarrow, liver, pancreas, collagen, or neovascularity or any tissue orcell culture which can be made to grow into the porosity of the implant.

A third example of the invention involves the use of fibers disposedwithin, or within and extending from, the porous section of the finalproduct, for reinforcing or changing the characteristics of the porosityof the final product. The construction of such a final product will nowbe described.

After mixing the sugar moldable mass, as in the first example (see FIG.1), commercially available fiberglass or carbon graphite fibers are cutto the desired length, for example, 1 cm., and mixed randomly with themoldable mass. The moldable mass is then placed in a container as beforeand allowed to solidify, forming the SRO-CPMF. For any given fiber, partof the fiber is within the sugar, either resting on a particle which hasbeen partially dissolved and subsequently has some additional sugardeposited and recrystallized on its surface, or within sugar depositedand solidified at the particle surface and/or the particle connection.Also for any given fiber, part of the fiber may not be in contact withsugar but rather simply extend into the voids of the SRO-CPMF. If aflexible reinforced porous section is desired in the final product,final product material, such as silicone rubber is selected. If a rigidfinal product is desired, polyester or epoxy resin, is introduced intothe voids of the SRO-CPMF as previously described. The part of the fiberwhich is exposed within the void becomes coated and incorporated withinthe matrix of the final product material. The sugar of the SRO-CPMF isthen dissolved so that that part of the fiber 41 (FIG. 4) within thesugar becomes exposed within voids 43 of the final device 45--theseexposed fibers can be ingrown by and fixed to tissue after implantation.

The proportion of fibers mixed into the SRO-CPMF may be varied greatlydepending on the stickiness availed to the particles within the SRO-CPMF(either inherently or by the binding medium used), and the wetability,diameter, and stiffness of the fiber itself. If the fiber to moldablemass particle ratio becomes too great, the moldable mass particlesbecome non-adherent to each other and the interconnecting open-cellednature of the SRO-CPMF breaks down, i.e., it can no longer be used as aporous mold form.

The length of the fibers used can also vary greatly. They can beoriented, pre-stretched or pre-woven, and placed within the containerbefore the introduction of the moldable mass to thereby fix theirposition, orientation, etc. within the SRO-CPMF, and thus within thefinal product. The fibers can also be disposed to extend out of theSRO-CPMF, and thus out of the voids of the final product and intonon-porous portions or outside the final product itself.

Similarly, a medical grade Dacron mesh (hole size about 1 mm) may beformed into a cylinder, for example, having a diameter about 2 mm lessthan the diameter of the inside walls of a container in which it isplaced. After placement in the container, a moldable mass is placed inthe container about and within the mesh cylinder, compacted, and allowedto solidify. This results in the mesh resting 1 mm from the containerwall within its circumference and within the SRO-CPMF, with sugarparticles and sugar particle connections being in continuity on eachside and through the mesh. The SRO-CPMF is then removed and placed intoanother container, for example about 1 mm larger in diameter than theSRO-CPMF. Final product material, such as catalyzed liquid siliconerubber, is then forced about and into the SRO-CPMF to a depth of, forexample, 2 mm and allowed to solidify (polymerize). The SRO-CPMF is thendissolved as described above and the ends of the tube are cut off. Theresulting prosthesis is inverted (turned inside out) yielding a devicewhich is smooth and non-porous to a depth of 1/2 mm on the inside, witha porous section to a depth of 2 mm on the outside. The central portionof the porous section is reinforced circumferentially by Dacron mesh,but with the porous section positioned on both sides and continuousthrough the mesh.

The device described above has been used a percutaneous cuff prosthesisfor artificial heart drive lines; it is slid over and glued to the linesat their exit point through the skin and this allows tissue ingrowth andfixation at and below the skin. Similar reinforced and fiber-modifiedporous prostheses have been made as vascular prostheses from medicalgrade blood compatible polyurethanes.

In the earlier example in which the sugar SRO-CPMF mold material wasremoved from the container before applying the liquid silicone rubber,one of the options for the final product was to make it porous on theinside and nonporous on the outside (FIGS. 3A and 3B). However, in manybiomaterial uses, it is desirable to have a porous section on theoutside and a nonporous section on the inside, in various shapes andratios. An example of the use for such a final product is a dorsal nasalaugmentation implant, and the process for fabricating such a finalproduct (as well as similar final products) will next be described.

The first step in the process is to form a positive model in the exactsize and shape of the desired final implant, made from substantially anymaterial although the clay-like thermoplastic material known as SculpeyModeling Compound has proven to be most satisfactory. Such material isformed and sculpted by hand or with molding tools into the desired shapeand then solidified by heating the material to 300 degrees F. for about15 to 20 minutes. A single positive model may be used to fabricate anumber of SRO-CPMF molds and therefore a number of final products, andthe thickness, position and shape of the porous versus non-poroussections may be controlled.

The positive model is then placed in a hinged rectangular container 44made of polyethylene (FIG. 5A), in one half of which is placed the moldmaterial for the SRO-CPMF 48 such as sugar moldable mass. The positivemodel 52 (in this case a nose implant) is then pressed partway into themold material 48 so that only its top (concave) surface is exposed. Athin layer of polyethylene sheeting or similar non-adhering material 56is then placed over the mold material 48 and positive model 52. Theother half of the hinged container is then filled (or overfilled) withsugar moldable mass 60 after which the container is closed, as shown inFIG. 5B, so that the moldable mass 60 is forced tightly over thesheeting 56 to conform to the shape of the exposed surface of thepositive model 52. The mold material 48 and 60 is then allowed to dry(solidify) and the two halves of the hinged container 44 are reopened toallow removal of the sheeting 56 and the positive model 52 to leave theSRO-CPMF 48 and 60 in place in the container. Alternatively, the hingedcontainer 144 could be first carefully opened, and the sheeting 56 andmodel 52 removed to allow drying of the moldable mass into the SRO-CPMF.

A medical grade elastomer such as RTV silicone rubber is then forcedinto the mold form 48 and 60 to a depth equal to the desired thicknessof the porous surface area of the final product. Silicone rubber is alsoplaced in the void in the mold material 48 and 60 left by the positivemodel 52 and then the container 44 is again closed, as shown in FIG. 5C.The silicone rubber is allowed to polymerize while in the mold 48 and 60of FIG. 5C after which the container 44 is opened, the mold formdissolved, and the final product implant removed to form a siliconerubber nasal implant having a solid interior 64 and a porous outsidesurface area 68 in FIG. 5D.

In addition to the above-described process for forming a nasal implantor similar final product, conventional injection molding techniques arealso effective in forming with the SRO-CPMF, by sintering sugar or otherremovable materials with heat and pressure in dies and molds in thedesired shapes and with the desired voids or models to create the voids.The final product material, i.e., silicone rubber, is then pressureinjected into the voids and into the mold form to the desired depth,with the same molds or dies used in forming the mold form or other diesor molds as needed. The resultant device using either process is apartially porous final product in which the locations and thicknesses ofthe porous section and the solid nonporous core and/or voids have beeneffectively controlled. A more viscous mass can be made by using cornsyrup rather than water as the sugar binding-dissolution medium and thiswill provide larger particle contacting in the mold form and thereforelarger pore interconnections in the final product. The viscosity of thefinal product material will also affect the porosity of the finalproduct when solidified. If a thick viscous silicone rubber solution isused, for example, then larger pores will be produced in the finalsilicone rubber product since the more viscous unpolymerized siliconerubber will contact the SRO-CPMF particles over less surface area toeffect incomplete surface molding. Also the pores will be smoother andmore rounded as will be the pore interconnections.

A doubly porous membrane (porous on each side but separated by animpermeable membrane) can be formed as in the steps just described forthe nose implant. Here, the process is essentially the same except thepositive model 52 (FIG. 5A and 5B) is eliminated; rather, the two halvesof the hinged container are closed over the nonadherent sheeting 56,causing the two opposing surfaces of the moldable mass material 48 and60 (separated by sheeting 56) to conform to each other. The hingedcontainer 44 is then opened, the sheeting 56 removed, and the moldmaterial 48 and 60 allowed to solidify. The final product material isthen placed between the two mold material 48 and 60 and then forcedthereinto to the depth desired. Upon curing, a final product as in FIG.6 of a nonporous membrane 65 with two porous surfaces 67 and 69 areproduced. The thickness of the non-porous membrane 65 can be controlledby controlling the thickness of the non-adherent sheeting 56 and thedegree to which the two opposing surfaces of the SRO-CPMF are forcedtogether. Complex shapes and implements such as tubes and externalsurfacing for use in artificial hearts and vessels, porous on one orboth sides, have been created in a similar manner utilizing silicone andbiocompatible polyurethanes.

Another example of a partially porous device made in accordance with thepresent invention is a breast implant. The beginning positive solidmodel, for example, polymethylmethacrylate formed with the desiredcurvatures and dimensions by machining or other suitable formingtechniques, is polished and cleaned so that there is no contamination.Then, as with the formation of the nose-bridge implant, a hingedrectangular container 74 (FIG. 7A) somewhat larger than the positivemodel 82 is filled with the sugar moldable mass 78 and 80 on each side.The polymethylmethacrylate breast implant model 82 is then pressedpartway into the moldable material 78, in one half of the container, sothat the upper convex surface of the model is exposed. A thin layer ofpolyethylene sheeting 86 or other thin, non-adhering sheeting materialis then placed over the model and the container 74 is closed tightlyover the polyethylene sheeting. The moldable mass 78 and 80 is thenallowed or caused to solidify as in the previous examples after whichthe container 74 is opened and the model 82 and the sheeting 86 removed.A medical grade elastomer 90 (FIG. 7B) is then forced into the SRO-CPMF78 and 80 to a depth equal to the desired thickness of the porouscoating of the resulting final product (any excess is drained offdepending on the desired thickness of the nonporous portion), afterwhich the parts of the container 74 are again closed tightly and theelastomer is allowed to polymerize. Additional coats of polymer may beapplied to the inside of the SRO-CPMF to build up the nonporous shellthickness of the final product to the desired specifications. (A smallhole must be left at some location if introduction of additional liquidform of the final product material into the void and onto and into thesurfaces of the mold forms 78 and 80 created by model 82, as will bediscussed momentarily, is needed.) The layers may be added before finalpolymerization, so that there may be no interfaces between the porousand nonporous portions or between the nonporous portions of the device.

The container 74 is again opened and the mold forms 78 and 80 aredissolved from the elastomer 90 by multiple washings, etc. The resultantbreast implant device seen in FIG. 7C is partially porous, having apredetermined thickness of porosity on the entire outside surface 94, anext interior layer of non-porous elastomer 98, and an interior void102. The void may be left or later filled with some type of material toprovide a breast implant with the desired feel, malleability andfunction. For example, the void 102 might be filled with a normal salinesolution to yield a saline-filled breast prosthesis. The void 102 mightalso be filled or partially filled with a semi-solid such as a partiallycross-linked silicone elastomer creating a silicone gel-filled implant.Finally, the void 102 could be filled with a catalyzed unpolymerizedelastomer and allowed to polymerize and fully cross-link to create arubbery, nonporous form with a porous covering. For some applications,it might be necessary to leave the void or to fill the void with a gassuch as air.

Another specific illustrative embodiment of the method of the presentinvention for making a breast implant involves use of a two-partpolyethylene mold 114 (FIG. 8A) defining a cavity 118 having an ovalcross-section, into which is placed the sugar moldable mass 122. Alsodisposed to extend from the mold form 122 through an opening in the mold114 is a handle 126 made of stainless steel or other stable,corrosive-resistant material. After forming, the SRO-CPMF 122 withattached handle 126 is removed from the mold 114.

Alternatively, to prepare the SRO-CPMF 122 of FIGS. 8A and 2B, thepolymethylmethacrylate model 82 of FIG. 7A affixed with stainless steelhandle 126 as in FIG. 8A, may be used by slightly roughening and/orcoating the surface of the model with corn syrup to encourage adherence,and then spraying the surface with specific sized sugar particles underair pressure, intimately mixed with a small amount of de-ionized water(in a manner similar to mixing gunite cement). The surface moistenedsugar particles, upon striking the model surface 82, adhere to the modeland to each other. The thickness of the layer of particles can becontrolled to produce a desired thickness sugar SRO-CPMF shell on theoutside of the model 82. This sugar shell would then be allowed to dryto form the SRO-CPMF as previously described in FIGS. 8A and 8B.

In either example above-described, the mold form is dipped into amedical grade silicone dispersion, by holding onto the handle 126 byhand. Vacuum application to the mold form 122 during or immediatelyafter dipping can increase the depth of penetration of the siliconedispersion and eliminate bubbles and coating irregularities within themold form. The mold form can be redipped into the silicone dispersion,after drying, from two to six times, depending on the desired thicknessof the silicone shell being formed. The first one or two times the moldform 122 is dipped into the dispersion, the silicone flows into thevoids in the mold form to develop what will ultimately be the porousportion of the device 138 (FIGS. 8C and 8D). The subsequent dipping ofthe mold form 122 will simply add nonporous layers 134 (FIGS. 8C and 8D)about the mold form. The thickness of the porous portion in the firstexample may be controlled by controlling the viscosity of the siliconedispersion and the amount of time and pressure or vacuum applicationduring or shortly after the initial coats, which in turn determines theextent of penetration of dispersion into the mold form 122 and in thesecond example by controlling the thickness of the SRO-CPMF shell on thepolymethylmethacrylate model 82.

After conclusion of the dipping steps, the silicone dispersion isvulcanized in an oven at, for example, 275 degrees F. for about onehour. Then a small (11/2 to 2 cm) hole 130 (FIG. 8B) is cut into thenonporous silicone covering around the dipping handle and then hot,de-ionized water is applied to the hole to reach and dissolve theSRO-CPMF material 122. Multiple washings may be required for this. Theresulting silicone device consists of a shell whose outer surface 134(FIG. 8C) is nonporous and whose inner surface 138 is porous. Thepositions of the nonporous and porous surfaces are reversed, however, byinverting the device through the hole 130 (FIG. 8D) formed to allowentry of hot water to dissolve the mold form 122, so that the porousportion 138 (FIG. 8D) of the device is now on the outside and thenonporous portion 134 (FIG. 8D) is on the inside. Of course, a void orcavity 142 is still present in either device in FIG. 8C or 8D.

To close the hole or opening 130, a small solid silicone patch 146 isglued with a medical grade silicone adhesive (or a patch of unvulcanizedsilicone rubber is vulcanized) in place over the opening. Of course, theouter patch surface 146 could be made either porous or nonporousdepending upon the need. Also, conventional self-sealing valves could beincluded in the patch 146 so that previously described materials couldbe inserted into the void 142 at any time.

Another example of the use of the present invention involves utilizingthe SRO-CPMF particles 150 (FIG. 9) within the final product material152 by leaving at least some of the SRO-CPMF material in the finalproduct to be dissolved over time, after implantation of the product ina person's body. In effect, the device becomes a drug delivery systemfor implantation in which the SRO-CPMF material consists of or includesdrugs to be delivered in or on the human body. Examples of such drugswhich might be included in a device during fabrication are gentamicin,tetracycline or cephalosporin crystals, but many other drugs availableor drugs which can be disposed in crystalline form could also be used.Most drugs such as antibiotics, which are usually supplied in a powderform, would be dissolved and recrystallized into larger crystals.Depending on their inherent stickiness and heat stability, the crystalswould then be partially dissolved and mixed and formed as a moldablemass or heated and compacted, to be used as the SRO-CPMF as describedfor sugar. (A filler medium such as dextrose crystals can be mixed withthe drug to get a smaller concentration of drug if needed.)Alternatively, the crystals can be bound together with a neutral,non-drug interacting, biologically compatible binding medium such as aconcentrated dextrose solution in a ratio of 1 part saturated dextrosesolution to between 4 and 40 parts drug crystal. Still anotheralternative is to dissolve or suspend the drug particles in powder formin the dextrose solution and then use this solution to coat otherparticles, such as another drug or dextrose crystals to form a SRO-CPMFwith precipitated dextrose and drug particles on the surface. Thedissolved or suspended drug within the dextrose solution may also berecrystallized, sized and made into a SRO-CPMF itself as in the previousexamples of sugar SRO-CPMF. Specifically, an example of such acombination would be the dissolution of gentamicin crystals in apharmaceutically pure saturated dextrose (sugar) solution,recrystallization and molding of these particles into a SRO-CPMF intowhich a silicone or other final product material is then placed.

Differing concentrations of drug in different layers (in the same mannerin which graduated sizes of particles are used in making a SRO-CPMF asin FIG. 3B) or different drugs in different layers may be producedwithin the SRO-CPMF mold material so that a different concentration of acertain drug, or a different drug will be encountered as ingrowthproceeds depending on the mechanism used by the body for removing theselected SRO-CPMF.

As indicated, the drug or drug infiltrated mass may be used as themoldable mass for the SRO-CPMF, and a biologically compatible materialsuch as Medical Grade Silicone Rubber used as the final productmaterial. An RTV (room temperature vulcanizing) silicone is thepreferred material for the final product so that the heat required forother forms of silicone won't be needed--such heat polymerization mightotherwise denature or alter the active form of the drug. Alternatively,a polyvinyl alcohol or polyglycolic or polylactic acid, or otherabsorbable final product material, might be used. To insure sterility,the fabrication of the SRO-CPMF is done under sterile conditions (allmaterials and appliances of fabrication are sterilized and the drug issupplied as sterile), or alternatively, the device is fabricated under"clean room" conditions and the device sterilized by accepted techniqueswhich do not alter the bio-activity of the drug. The device is thenimplanted in or placed on the human body, or into a body cavity, toallow tissue to grow into or fluids to penetrate, so that the body willpassively and/or actively dissolve the SRO-CPMF to cause release of thedrug. Again, the prevention of the thick capsule formation and the lackof isolation of the vascularity from the implant, characteristics whichcan be built into the porous portion of the device with theabove-described methods, is an important key to the success of such animplanted device. By controlling the size of the implant, the amount ofsurface area of porosity exposed for passive dissolution or tissueingrowth, the size of the pores, the size of the pore interconnections,the concentration of the drug in the SRO-CPMF, the water-soluble versusfat soluble form of the drug, and the site of implantation, control ofthe pharmacokinetics are made possible. Also, a combined device wheredrugs are incorporated into both the SRO-CPMF and the final productmaterial resulting in a biphasic adsorption can be made by physicallymixing the drug particles or using concentrated drug solutions andmixing them with the final product material and processing them asdescribed above.

Another example of the use of the present invention involves productionof a porous metal or metallic alloy device 154 (FIG. 10), which in thisexample includes a nonporous section 156 and a porous section 158, foruse in or on the human body as an electrode or battery plate, etc. Toproduce metallic partially porous devices, the sugar SRO-CPMF is firstvacuum-impregnated with wax. The SRO-CPMF is then removed by dissolutionand dried. A conventional ceramic refractory material, taking the placeof the SRO-CPMF, is then vacuum-impregnated into the wax. The metal,such as silver, gold, Vitallum or other castable metals are then heatedto their molten phase and cast into the negative wax replica of theSRO-CPMF made by ceramic refractory material, by standard centrifugalcasting techniques taking the place of the wax. This creates the sameporous form as would have resulted if silicone rubber had beenintroduced into the SRO-CPMF as described earlier, but out of metal.

To create ceramic partially porous devices, the SRO-CPMF is vacuumimpregnated with wax as above, the SRO-CPMF dissolved, and the waxdried. A concentrated suspension of fine particle-sized (5 mm) ceramic,e.g., α-alumina, is then vibrated into the pores of the wax open-cellporous mold form, and the ceramic is allowed to dry. The combination ofthe wax mold form and ceramic are then heated to about 400 degrees C.and the wax allowed to melt and/or burn off. The ceramic is thensintered at 1650-1700 degrees C. The porosity this time is the negativereplica of the SRO-CPMF, with the sintered ceramic essentially resultingin a duplicate of the SRO-CPMF.

With the above type construction techniques with sugars, waxes,refractories and other selectively removable materials serving as theSRO-CPMF or filling the spaces between the SRO-CPMF, positive ornegative copies of the SRO-CPMF can be created. All of the otherpreviously described control techniques as to porous and non-porousportions, size and position of the open-cell surface area, etc. areapplicable to producing the metallic or ceramic devices described. Thesedevices, as already mentioned, could be used in a variety of situationswhere large surface area exposure of the device is desired.

Another example of the use of the method of the present inventioninvolves construction of a device as with any of the previous examplesbut adapted for use as a dialysis device or a blood oxygenation device.These devices utilize a doubly porous membrane such as illustrated inFIG. 11. Mold form material 164 is created as described with any of theabove methods. The liquid phase final product material (illustrativelyRTV silicone rubber) is then forced into the interstices of the moldform 164. Then, most of the silicone rubber is forced out of theinterstices of the mold form by a liquid or gas, such as compressednitrogen gas, leaving the mold form with a very thin coat of thesilicone rubber 162. This reproduces the open-celled structure on theside of the silicone rubber coat or membrane, opposite the location ofthe mold form material--forms a secondary porosity 160 (see FIG. 11).The next step in the process, as described earlier, is to cure orpolymerize the silicone rubber 162 and to dissolve out the mold formmaterial 164 creating the primary porosity (where the mold form materialwas). It is helpful to use some kind of surfactant such as a weak soapsolution in both the solution dissolving out the mold form material andon the secondary porosity side to prevent adherence of the siliconerubber to itself which would close off the porosities thus created.

When the dissolution of the mold form material is complete, thereremains a doubly porous silicone rubber membrane 162, with nocommunication between the two porosities. The primary porosity 164(visualized without the mold form material) on the one side of themembrane 162 has its porosity, created by the mold form, whereas thesecondary porosity 160 on the other side of the membrane has itsporosity created by removing much of the silicone rubber within theinterstices of the mold form. This side of the membrane may then beisolated by standard molding or construction techniques so that a gas,such as oxygen, or a liquid, such as a kidney dialysis solution, can becirculated through this secondary porosity, without cross-circulationinto the primary porosity. Such a device may then be implanted so thatthe primary porosity 164 is filled intimately with new blood vessels andloose connective tissue. It has been found that this device is verytissue-compatible, with no fibrosis developing within the primaryportion, and with capillaries and blood vessels literally within closeproximity of the silicone rubber membrane.

With the prosthesis described above used as a dialysis device, astandard dialysis solution would be circulated through the secondaryporosity 160. The membrane 162 between the porosities 160 and 164 actslike a dialysis membrane in a standard artificial kidney, removing theunwanted ureas, nitrogen compounds and ions, based on the standarddiffusion principles. Due to the large surface area of the primaryporosity, and the fact that a capsule doesn't form between theneovascularity and the silicone rubber membrane, an implantable dialysisdevice is now made practical.

Likewise, a similar device may be constructed for use in bloodoxygenation. The device would be implanted and a specific oxygenconcentration circulated through the secondary porosity 160. This time,with the thin silicone rubber membrane 162 acting as a gas transfermembrane, oxygen is transferred into the capillaries and vessels ingrownin the primary porosity 164 and carbon dioxide is removed from thevessels into the circulating oxygen in the secondary porosity 160. Thecarbon dioxide is then subsequently removed.

Using the previous example, a layered membrane or a final product with alayer coating, such as shown in FIG. 12, may be created as follows.After the thin membrane of the final product of silicon rubber 170 hasbeen applied to the mold form, as in the previous example, and cured,but before the mold form is removed, a secondary material in its liquidform, e.g., a Biomer polyurethane solution 174 is vacuum impregnatedinto the secondary porosity. This may either be partially blown out asdescribed for forming the membrane in the previous example, or a thin(i.e., 10 to 15 percent) solution of the Biomer may be vacuumimpregnated and dried (resulting in removal of the 85 to 90 percentsolvent) in an oven at 50 degrees C. for two hours. This leaves adouble-layered, interlocking membrane with separate porosity on eachside, as shown in FIG. 12.

Similarly, the physical interweaving of two materials processed as abovecan be used to advantage in joining two dissimilar materials (which donot readily adhere) to each other. This can be done so that there isdouble porosity left as in the FIG. 12 example. Two other methods canalso be used to join the two materials, and give a porous or a nonporoussurface on one side. Using the example described for FIG. 11, the thinsilicone rubber membrane is applied to the mold form and cured, but themold form is kept in place. The next material, say a catalyzed polyesterresin, is vacuum impregnated into the secondary porosity and allowed topolymerize. The mold form is removed, resulting in a nonporous polyestersurface and polyester interlocking structure in intimate contact withthe thin silicone membrane, with porosity on the side of the membraneaway from the polyester resin.

In a similar manner, two sheets or structures can be joined utilizingthe porosity. This is done by creating a partially porous sheet ofsilicone rubber, as described in the example accompanying FIG. 6, havinga nonporous section 186 (FIG. 13) and a porous section 184. Afterdrying, a catalyzed polyester resin is vacuum impregnated into theporosity of the silicone rubber. After polymerization, the resultantstructure has two nonporous surfaces, 186 for the silicone rubber 186,and 180 for the polyester resin, with their associated porosities 184and 182 respectively being in intimate contact mechanically to interlockthe two materials together.

It is to be understood that the above-described arrangements are onlyillustrative of the application of the principles of the presentinvention. Numerous modifications and alternative arrangements may bedevised by those skilled in the art without departing from the spiritand scope of the and the appended claims are intended to cover suchmodifications and arrangements.

I claim:
 1. A method of forming a selectively removable open-cell porousmold form comprising the steps of:(a) obtaining particles having sizesin the range of about 25-600 microns, said particles comprising amaterial capable of self-adhering when exposed to a first selectedcondition, solidifying when exposed to a second selected condition, anddesolidifying when exposed to a third selected condition; (b) exposingsaid particles to a first selected condition such that the particlesadhere into a mass of continuously interconnected particles definingcontinuously interconnected pores, said pores being each connected to atleast one adjacent pore by pore interconnections and said pores and poreinterconnections having a substantially smoothly flowing configuration;(c) forming said mass of continuously interconnected particles into apredetermined shape; and (d) exposing said formed and shaped mass to asecond selected condition to solidify said mass into a selectivelyremovable mold form for use in preparing devices having a porous portioncorresponding to said continuously interconnected and substantiallysmoothly flowing pores and pore interconnections.
 2. The method of claim1 wherein the particles obtained in step (a) comprise a materialselected from the group consisting of polymers, ceramics, metals,biological derivatives and combinations thereof.
 3. The method of claim1 wherein the particles obtained in step (a) comprise a porous material.4. The method of claim 1 wherein step (b) comprises the selectedcondition of adding a liquid to a solid phase of said particles tothereby affect the binding between the particles.
 5. The method of claim4 wherein said solid phase is dissolvable in said liquid such thatpartial dissolution of said solid phase is achieved.
 6. The method ofclaim 5 wherein the liquid comprises water and the solid phase comprisessugar.
 7. The method of claim 5 wherein the liquid comprises saturatedsugar solution and the solid phase comprises sugar.
 8. The method ofclaim 4 wherein step (d) comprises the second selected condition ofremoving the liquid.
 9. The method of claim 1 wherein the particlesobtained in step (a) are crystals and step (d) comprises the secondselected condition of effecting crystallization of said particles. 10.The method of claim 1 wherein step (b) comprises the selected conditionof heating a solid phase of said particles to thereby affect the bindingbetween the particles.
 11. The method of claim 10 wherein step (d)comprises the second selected condition of cooling of said particles.12. The method of claim 1 wherein the particles are coated with aselected material, said coating material being capable of self-adheringwhen exposed to a first selected condition and capable of solidifyingwhen exposed to a second selected condition.
 13. The method of claim 12wherein the particles are coated with sugar.
 14. The method of claim 12wherein the particles are coated with a polymerizable material.
 15. Themethod of claim 14 wherein step (d) comprises the second selectedcondition of effecting polymerization of said coating.
 16. The method ofclaim 1 comprising the further step of mixing fibers into the particlesobtained in step (a) such that portions of fibers extend into the poresand pore interconnections of the solidified mold form.
 17. The method ofclaim 16 wherein the fibers comprise fiberglass or carbon graphitefibers.
 18. The method of claim 2 wherein the particles comprise athermoplastic polymer.
 19. The method of claim 18 whereto thethermoplastic polymer is selected from the group consisting of waxes,paraffins, polyethylenes, nylons, polycarbonates, and polystyrenes. 20.The method of claim 1 wherein the particles comprise a pharmaceuticalcomposition.
 21. An open-cell porous mold form made by the method ofclaim 1.